Electromagnetic (EM) fields cause many changes in cells, but no known mechanisms link cellular changes to health risks. A possible link to disease is the stress response in cells, a know reaction to harmful stimuli that is activated by EM fields. However, it is not known how EM fields initiate this response. Information about physical transduction mechanisms is needed to understand the link to disease, and to define relevant exposure parameters in a hazard assessment model. Studies of mechanism that have identified thresholds and molecular processes in physical transduction, have been based on Na,K-ATPase function in separate electric and magnetic fields. The dependence of both field effects on enzyme activity indicates that the initial reactions appear to be related to charge movements during enzyme function. Differences between the field effects can be explained by the different degrees of penetration of the individual field into cells. To continue this research with greater control of charge movements, the proposed mechanism will be tested with cytochrome oxidase, a well defined electron transport enzyme in the mitochondrial oxidation chain. Techniques for assaying and controlling electron flow in cytochrome oxidase activity, as well as the instrumentation to control exposure electron flow to cytochrome oxidase activity, as well as the instrumentation to control exposure to electric and magnetic fields, will be used to study the role of charge movements during signal transduction and to define thresholds. The long-term objective is to characterize the mechanism of EM field signal transduction by cells and to determine environmentally relevant exposure parameters. Knowledge of the mechanism will clarify the relation between EM field exposure and disease-related changes in cells. It will then be possible to define relevant parameters in a hazard assessment model. The specific aims of this study are to determine: a. the relation between changes in cytochrome oxidase function in electric and magnetic fields, and the rate of electron transport. b. the electric and magnetic field threshold for changes in cytochrome oxidase function.